the human's body toward medical applications. [1] Coupling electronics with human tissues allows sensing, stimulating and possibly regulating biological functions. On these premises, a key paradigm of bioelectronics is to preserve the functionality of the biological environment upon coupling, in order to "observe biology through non-perturbing lenses". However, aiming to a seamless interface, the properties of common electronic components, based on metals or inorganic semiconductors, have major limitations to comply with the coupling requirements for cells, organs, and tissues. [2] In fact, inorganic materials might display mechanical rigidity (high Young's modulus ≈100 GPa), [3,4] surface degradation phenomena (oxidation) [5] and surface structure which increases interface capacitance. [6,7] Organic materials have so emerged combining mechanical flexibility, compatibility with large area and different surface functionalization processes, while keeping high electrical conductivity and reproducibility. [8,9] Particularly, these materials intrinsically display key properties such as tunable surface roughness, [10] surface chemical reactivity 11 , and Young's moduli ranging from 20 kPa to 3 GPa, [11,12] approaching the modulus of living tissue (10 kPa [13] ). However, the diversity of biological landscapes offered by the different human tissues, in terms of mechanical flexibility, interface functionalization, accessibility and biological activities defines sets of requirements so stringent that commonly for each tissue/organ coupling ad hoc devices and platforms have been developed. Hence, examining the three major human's body interfaces targeted by bioelectronics applications (skin, heart, and brain), this review focuses on the strategies that can be adopted by employing organic materials such as surface patterning, novel material synthesis and bio-functionalization in order to enhance tissue/organ-specific coupling performances. These aspects are investigated highlighting current and future main challenges and providing perspectives on the development of the next generation organic bioelectronics devices, thus envisioning systems that are: 1) able to adapt their interface in shape and size to comply with different curvilinear and hierarchical biological architectures and 2) combine sensing and stimulation to dynamically control biological functions for biomedical applications.